Various omega-3 fatty acids and uses thereof, including in pharmaceutical, nutritional or dietary supplement products, are known in the art. See, e.g., U.S. Pat. Nos. 5,502,077, 5,656,667 and 5,698,594.
One pharmaceutical product is known as LOVAZA® (active name “omega-3-acid ethyl esters”), a lipid-regulating agent approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglyceride levels in adult patients with very high (>500 mg/dL) triglyceride levels, at a dose of 4 g per day (either as a single 4-g dose (4 capsules) or as two 2-g doses (2 capsules given twice daily)).
LOVAZA® is marketed as a liquid-filled gel capsule for oral administration. Each 1 gram capsule of LOVAZA® contains at least 900 mg of ethyl esters of omega-3 fatty acids. These are predominantly a combination of ethyl esters of EPA (approximately 465 mg) and DHA (approximately 375 mg). LOVAZA® capsules also contain the inactive ingredients: 4 mg α tocopherol (in a carrier of vegetable oils including soybean oil), and gelatin, glycerol, and purified water (components of the capsule shell).
The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, NIH Publication No. 02-5215 (September 2002) (also known as the “NCEP ATP III”), Guidelines classify triglycerides as normal (<150 mg/dL), borderline high (150-199 mg/dL), high (200-499 mg/dL), and as very high (≧500 mg/dL). While LOVAZA® has demonstrated efficacy in reducing triglycerides in the very high triglyceride population, for many patients, their triglycerides remain above normal levels.
It would be advantageous to increase the therapeutic effect of omega-3 fatty acid compositions such as LOVAZA®, e.g. to provide improved methods of treatment such as reducing elevated triglycerides. One approach to increasing the therapeutic effect of orally-administered drugs is to increase the exposure or absorption of the drug after oral administration. It may therefore be advantageous to increase the exposure of omega-3 fatty acids following oral administration. It would be particularly advantageous if an increased therapeutic effect could be provided without increasing the burden of administration, such as pill or capsule burden, e.g., maintaining or even reducing the dosage amount and/or frequency, e.g. the number and/or size of capsules. Reducing the administration burden may, for example, allow for easier administration, improve patient compliance, reduce side effects such as eructation, reduce caloric intake, reduce exposure to any undesired components which may be present in some omega-3 products, and/or reduce cost of therapy.
The literature includes various references which disclose studies involving fish oil and/or omega-3 fatty acid compositions, which in some instances may be emulsified or emulsifiable compositions. See, e.g., Garaiova et al. Nutrition Journal 2007, 6:4 (http://www.nutritionj.com/contents/6/1/4); Raatz et al. Jnl of the American Dietetic Association June 2009 Vol 109 No. 6 1076-1081; Mishra et al. U.S. Pat. No. 6,284,268, issued Sep. 4, 2001; WO2008/101344; and Bryhn, M. et al., Prostaglandins, Leukotrienes and Essential Fatty Acids 75:19-24 2006.